Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis

AbstractIntroductionThis meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals.MethodMEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, were considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen's d.ResultsA total of 38 studies met inclusion criteria contributing 30 cross-sectional (N = 5005) and 14 longitudinal (N = 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d = 0.32), visuospatial function (d = 0.25), processing speed (d = 0.18), episodic memory, and executive function (both d's = 0.15), with decline observed for global cognition (d = 0.30), semantic memory (d = 0.28), visuospatial function (d = 0.25), and episodic memory (d = 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used.DiscussionCN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition

A Semantic analysis of control

This thesis examines the use of denotational semantics to reason about control flow in sequential, basically functional languages. It extends recent work in game semantics, in which programs are interpreted as strategies for computation by interaction with an environment. Abramsky has suggested that an intensional hierarchy of computational features such as state, and their fully abstract models, can be captured as violations of the constraints on strategies in the basic functional model. Non-local control flow is shown to fit into this framework as the violation of strong and weak `bracketing' conditions, related to linear behaviour. The language muPCF (Parigot's mu_lambda with constants and recursion) is adopted as a simple basis for higher-type, sequential computation with access to the flow of control. A simple operational semantics for both call-by-name and call-by-value evaluation is described. It is shown that dropping the bracketing condition on games models of PCF yields fully abstract models of muPCF. The games models of muPCF are instances of a general construction based on a continuations monad on Fam(C), where C is a rational cartesian closed category with infinite products. Computational adequacy, definability and full abstraction can then be captured by simple axioms on C. The fully abstract and universal models of muPCF are shown to have an effective presentation in the category of Berry-Curien sequential algorithms. There is further analysis of observational equivalence, in the form of a context lemma, and a characterization of the unique functor from the (initial) games model, which is an isomorphism on its (fully abstract) quotient. This establishes decidability of observational equivalence for finitary muPCF, contrasting with the undecidability of the analogous relation in pure PCF

Supporting user-oriented analysis for multi-view domain-specific visual languages

This is the post-print version of the final paper published in Information and Software Technology. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2008 Elsevier B.V.The integration of usable and flexible analysis support in modelling environments is a key success factor in Model-Driven Development. In this paradigm, models are the core asset from which code is automatically generated, and thus ensuring model correctness is a fundamental quality control activity. For this purpose, a common approach is to transform the system models into formal semantic domains for verification. However, if the analysis results are not shown in a proper way to the end-user (e.g. in terms of the original language) they may become useless. In this paper we present a novel DSVL called BaVeL that facilitates the flexible annotation of verification results obtained in semantic domains to different formats, including the context of the original language. BaVeL is used in combination with a consistency framework, providing support for all steps in a verification process: acquisition of additional input data, transformation of the system models into semantic domains, verification, and flexible annotation of analysis results. The approach has been validated analytically by the cognitive dimensions framework, and empirically by its implementation and application to several DSVLs. Here we present a case study of a notation in the area of Digital Libraries, where the analysis is performed by transformations into Petri nets and a process algebra.Spanish Ministry of Education and Science and MODUWEB

DeltaImpactFinder: Assessing Semantic Merge Conflicts with Dependency Analysis

In software development, version control systems (VCS) provide branching and merging support tools. Such tools are popular among developers to concurrently change a code-base in separate lines and reconcile their changes automatically afterwards. However, two changes that are correct independently can introduce bugs when merged together. We call semantic merge conflicts this kind of bugs. Change impact analysis (CIA) aims at estimating the effects of a change in a codebase. In this paper, we propose to detect semantic merge conflicts using CIA. On a merge, DELTAIMPACTFINDER analyzes and compares the impact of a change in its origin and destination branches. We call the difference between these two impacts the delta-impact. If the delta-impact is empty, then there is no indicator of a semantic merge conflict and the merge can continue automatically. Otherwise, the delta-impact contains what are the sources of possible conflicts.Comment: International Workshop on Smalltalk Technologies 2015, Jul 2015, Brescia, Ital

The neural correlates of semantic control revisited.

Semantic control, the ability to selectively access and manipulate meaningful information on the basis of context demands, is a critical component of semantic cognition. The precise neural correlates of semantic control are disputed, with particular debate surrounding parietal involvement, the spatial extent of the posterior temporal contribution and network lateralisation. Here semantic control is revisited, utilising improved analysis techniques and a decade of additional data to refine our understanding of the network. A meta-analysis of 925 peaks over 126 contrasts illuminated a left-focused network consisting of inferior frontal gyrus, posterior middle temporal gyrus, posterior inferior temporal gyrus and dorsomedial prefrontal cortex. This extended the temporal region implicated, and found no parietal involvement. Although left-lateralised overall, relative lateralisation varied across the implicated regions. Supporting analyses confirmed the multimodal nature of the semantic control network and situated it within the wider set of regions implicated in semantic cognition

Disruption of semantic metwork in mild Alzheimer's disease revealed by resting-state fMRI

Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients even in the early stages of the illness. In this work, we tested the hypothesis that the semantic control network is deregulated in mild AD patients. We assessed the integrity of the semantic control system using resting-state functional magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean mini-mental state examination = 20.5) and in a group of age-matched healthy controls (n = 19). Voxel-wise analysis spatially constrained in the left fronto-temporal semantic control network identified two regions with altered functional connectivity (FC) in AD patients, specifically in the pars opercularis (POp, BA44) and in the posterior middle temporal gyrus (pMTG, BA21). Using whole-brain seed-based analysis, we demonstrated that these two regions have altered FC even beyond the semantic control network. In particular, the pMTG displayed a wide-distributed pattern of lower connectivity to several brain regions involved in language-semantic processing, along with a possibly compensatory higher connectivity to the Wernicke's area. We conclude that in mild AD brain regions belonging to the semantic control network are abnormally connected not only within the network, but also to other areas known to be critical for language processing